Unveiling the principle of microRNA-mediated redundancy in cellular pathway regulation

RNA Biol. 2015;12(3):238-47. doi: 10.1080/15476286.2015.1017238.

Abstract

Understanding the multifaceted nature of microRNA (miRNA) function in mammalian cells is still a challenge. Commonly accepted principles of cooperativity and multiplicity of miRNA function imply that individual mRNAs can be targeted by several miRNAs whereas a single miRNA may concomitantly regulate a subset of different genes. However, there is a paucity of information whether multiple miRNAs regulate critical cellular events and thereby acting redundantly. To gain insight into this notion, we conducted an unbiased high-content miRNA screen by individually introducing 1139 miRNA mimics into Chinese hamster ovary (CHO) cells. We discovered that 66% of all miRNAs significantly impacted on proliferation, protein expression, apoptosis and necrosis. In summary, we provide evidence for a substantial degree of redundancy among miRNAs to maintain cellular homeostasis.

Keywords: 3'-untranslated region; 3'UTR; AF647; AlexaFluor→647; CH; CHO; CO2; Chinese hamster; Chinese hamster ovary; Cricetulus griseus; MIR; PI; RNA interference; RNAi; SEAP; base pair; bp; cDNA; carbon dioxide; cgr; chinese hamster ovary; mRNA; mature microRNA; miR; miRNA; microRNA; nc; non-coding; pathway regulation; pre-miR; precursor microRNA; propidium iodide; puro; puromycin; qRT-PCR; quantitative reverse-transcriptase real-time PCR; redundancy; rounds per minute; rpm; screen; secreted alkaline phosphatase; siRNA; small-interfering RNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • CHO Cells
  • Cell Proliferation
  • Cofilin 2 / antagonists & inhibitors
  • Cofilin 2 / genetics
  • Cofilin 2 / metabolism
  • Cricetulus
  • Gene Expression
  • Gene Expression Profiling
  • Homeostasis / genetics
  • Metabolic Networks and Pathways / genetics*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Mimicry
  • Necrosis / genetics
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Transfection

Substances

  • Cofilin 2
  • MicroRNAs
  • RNA, Messenger
  • RNA, Small Interfering